Pyrimidine-pyrimidone (6-4) photoproduct ((6-4)PP) ((6-4)PP)

Pyrimidine-pyrimidone (6-4) photoproducts are a primary form of DNA damage caused by exposure to ultraviolet (UV) radiation, specifically UV-B and UV-C wavelengths. These lesions are formed by a covalent bond between the C6 position of a 5' pyrimidine and the C4 position of the adjacent 3' pyrimidine, resulting in a significant structural distortion of the DNA helix (Sinha & Hader, 2002). Although they occur less frequently than cyclobutane pyrimidine dimers (CPDs), (6-4)PPs are highly mutagenic and can lead to C-to-T transitions, which are characteristic UV-signature mutations found in skin cancers (Brash, 2015). In humans, these lesions are exclusively repaired by the nucleotide excision repair (NER) pathway, and a failure to repair them is a hallmark of Xeroderma pigmentosum (DiGiovanna & Kraemer, 2012). From a therapeutic perspective, (6-4)PPs are the targets of exogenous DNA repair enzymes, such as photolyases and T4 endonuclease V, which are incorporated into topical treatments to reduce the risk of skin cancer and actinic keratosis (Stege et al., 2000). These enzymes work by either direct reversal of the lesion using light energy or by initiating the repair process in cells with compromised endogenous repair mechanisms.

Other names

6-4 photoproduct(6-4) pyrimidine-pyrimidone dimer6-4PPUV-induced DNA lesion

Direct reversal of DNA damage via photo-enzymatic repair (photolyases) or enzymatic incision of the DNA backbone to initiate nucleotide excision repair (T4 endonuclease V).